Sorooshian S S, Stafford M A, Eastwood N B, Boyd A H, Hull C J, Wright P M
Department of Anaesthesia, University of Newcastle-upon-Tyne, United Kingdom.
Anesthesiology. 1996 May;84(5):1083-91. doi: 10.1097/00000542-199605000-00010.
The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect.
Thirty-one young (18-50 yr) and 33 elderly ( > 65 yr) patients anesthetized with nitrous oxide, isoflurane, and fetanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracurium was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after supramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five venous blood samples were obtained for plasma drug concentration at intervals ranging from 2 to 120 min from every patient. Three additional samples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concentration and effect data. The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults.
Onset of block was delayed in the elderly; values being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2.4-6.5) min in the young and elderly, respectively (P < 0.01). Duration of action was similar in the two groups. Plasma clearance was 319 (293-345) ml/min in the study population and did not differ between young and elderly patients. Apparent volume of distribution was 13.28 (9.9-16.7) 1 and 9.6 (7.6-11.7) 1 in the elderly and young adults, respectively (P < 0.05). There also were differences in pharmacodynamic parameters between the young and elderly; the predominant change being a slower rate of biophase equilibration (ke0) in the elderly (0.060 [0.052-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0.05).
The pharmacokinetics of cisatracurium differ only marginally between young and elderly adults. Onset is delayed in the elderly because of slower biophase equilibration.
由于多种原因，肌肉松弛剂对老年患者的作用可能与年轻成年患者不同。作者比较了一种新型肌肉松弛剂（顺式阿曲库铵）在年轻和老年成年人中的作用，并使用药代动力学/药效学模型来确定解释效应时间过程差异的因素。
研究了31名年龄在18至50岁的年轻患者和33名年龄大于65岁的老年患者，这些患者均接受氧化亚氮、异氟烷和芬太尼麻醉。麻醉诱导后给予顺式阿曲库铵（0.1mg/kg），随后追加0.025mg/kg的推注剂量或给予顺式阿曲库铵输注。在尺神经以2Hz频率进行超强刺激后，每隔15秒使用拇内收肌的四个成串刺激中的第一个颤搐来测量神经肌肉传递。从每位患者每隔2至120分钟采集5份静脉血样本以测定血浆药物浓度。对于接受输注的患者，额外采集3份样本。将群体药代动力学/药效学模型拟合到血浆浓度和效应数据。允许模型参数随年龄变化，以确定年轻和老年成年人之间存在差异的地方。
老年患者的阻滞起效延迟；年轻和老年患者的平均起效时间分别为3.0（95%置信区间1.75 - 11.4）分钟和4.0（2.4 - 6.5）分钟（P < 0.01）。两组的作用持续时间相似。研究人群的血浆清除率为319（293 - 345）ml/分钟，年轻和老年患者之间无差异。老年和年轻成年人的表观分布容积分别为13.28（9.9 - 16.7）升和9.6（7.6 - 11.7）升（P < 0.05）。年轻和老年患者在药效学参数方面也存在差异；主要变化是老年患者的生物相平衡速率（ke0）较慢（0.060 [0.052 - 0.068]）/分钟，而年轻患者为（0.071 [0.065 - 0.077]）/分钟；P < 0.05。
顺式阿曲库铵在年轻和老年成年人中的药代动力学仅存在微小差异。老年患者起效延迟是因为生物相平衡较慢。
